Biochemical mechanisms of the energy-protective action of blockers of slow high-threshold L-type calcium channels

Abstract

This review discusses information about the structure and function of calcium channels in the plasma membrane and mitochondria of the heart, and pharmacological methods for modulating their conductance. Experimental data are presented that characterize the change in the energy metabolism of cardiomyocytes against the background of the transformation of the conductivity of L-type calcium channels of the cell membrane in a non-invasive model of vibration-mediated (56 sessions of total vertical vibration, with a frequency of 44 Hz and an amplitude of 0.5 mm) hypoxia.

It was shown that in animals treated with calcium channel blocker adalat (nifedipine INN) against the background of vibration, the rate of endogenous respiration (V_e), measured by the polarographic method using a closed Clark electrode in native homogenate of rabbit myocardial tissue, remained at the level of intact animals and amounted to 16.3 ± 4.3 ng-O atom/ min · mg of protein, amytal sensitivity increased by 39% (p < 0.05) compared to the group of vibrated animals, low-natality decreased by 40% (p < 0.05). The dynamics of the rate of substrate respiration (V_ac and V_{glu + mal}) in the group with adalat returned to that of intact animals, which indicated the restoration of the physiological predominance of the activity of theNADH – CoQ-reductase complex in redox reactions. It was found that the blockade of transport of Ca²⁺ ions at the level of high-threshold (HVA) voltage-dependent ion channels of the L-type of the cell membrane, normalizing the activity of the I enzyme-substrate complex of the respiratory chain and regulatoryly restraining the hyperactivity of succinate dehydrogenase in zone II of the enzyme-substrate complex, has an energy-protective effect. Adalat prevented a low-energy shift and the development of bioenergetic hypoxia in the myocardial tissue of experimental animals.

Keywords

mitochondria / high threshold (HVA) voltage-gated L-type ion channels / cardiac canalopathy / model of vibration-mediated tissue hypoxia / polarography / calcium channel blockers / adalat / energy protection

References

[1] Biological membranes. Twelve essays on their organization, properties, and functions. Edited by Parsons DS. Clarendon Press, Oxford; 1975. 206 p.

[2] Biological membranes. Twelve essays on their organization, properties, and functions. Edited by D.S. Parsons. Clarendon Press, Oxford, 1975. 206 p.

[3] Belosludcev KN, Dubinin MV, Belosludceva NV, Mironova GD. Mitochondrial Са2+ transport: mechanisms, molecular structures, and role in cells. Biocyemistry. 2019;84(6):759–775. (In Russ.) DOI: 10.1134/S03209725190600022

[4] Белослудцев К.Н., Дубинин М.В., Белослудцева Н.В., Миронова Г.Д. Транспорт ионов Са2+ миохондриями: механизмы, молекулярные структуры и значение для клетки // Биохимия. 2019. Т. 84, № 6. С. 759–775. DOI: 10.1134/S0320972519060022

[5] Shishkina LN, Klimovich MA, Kozlov MV. A new approach to analysis of participation of oxidative processes in regulation of metabolism in animal tissues. Biophysics. 2014;59(2):904–909. (In Russ.) DOI: 10.1134/S0006350914020249

[6] Шишкина Л.Н., Климович М.А., Козлов М.В. Новый подход к анализу участия окислительных процессов в регуляции метаболизма в тканях животных // Биофизика. 2014. Т. 59, № 2. С. 380–386. DOI: 10.1134/S0006350914020249

[7] Kir’yakov VA, Pavlovskaya NA, Lapko IV, et al. Impact of occupational vibration on molecular and cell level of human body. Russian Journal of Occupational Health and Industrial Ecology. 2018;9:34–43. (In Russ.) DOI: 10.31089/1026-9428-2018-9-34-43

[8] Кирьяков В.А., Павловская Н.А., Лапко И.В., и др. Воздействие производственной вибрации на организм человека на молекулярно-клеточном уровне // Медицина труда и промышленная экология. 2018. Т. 9. С. 34–43.DOI: 10.31089/1026-9428-2018-9-34-43

[9] Kostyuk IF, Kapustnik VA. Role of intercellular calcium metabolism in vasospasm formation during vibration disease. Russian Journal of Occupational Health and Industrial Ecology. 2004;(7):14–17. (In Russ.)

[10] Костюк И.Ф., Капустник В.А. Роль внутриклеточного обмена кальция в развитии вазоспастических реакций при вибрационной болезни // Медицина труда и промышленная экология. 2004. № 7. С. 14–17.

[11] Tret’yakov SV, Shpagina LA. Prospects of studying structural and functional state of cardiovascular system in vibration disease patients with arterial hypertension. Russian Journal of Occupational Health and Industrial Ecology.2017;12:30–34. (In Russ.)

[12] Третьяков С.В., Шпагина Л.А. Перспективы изучения структурно-функционального состояния сердечно-сосудистой системы у больных вибрационной болезнью в сочетании с артериальной гипертензией // Медицина труда и промышленная экология. 2017. № 12. С. 30–34.

[13] Korotenko OYu, Panev NI, Korchagina YuS, et al. Fotmation of pathology of internal organs in miners with vibration disease. Russian Journal of Occupational Health and Industrial Ecology. 2020;60(6):399–403. (In Russ.) DOI: 10.31089/1026-9428-2020-60-6-399-403

[14] Коротенко О.Ю., Панев Н.И., Корчагина Ю.С., и др. Формирование патологии внутренних органов у шахтеров с вибрационной болезнью // Медицина труда и промышленная экология. 2020. Т. 60, № 6. С. 399–403.DOI: 10.31089/1026-9428-2020-60-6-399-403

[15] Meregalli P, Wilde A, Tan H. Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more? Cardiovasc Res. 2005;67(3):367–378.DOI: 10.1016/j.cardiores.2005.03.005

[16] Meregalli P., Wilde A., Tan H. Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more? // Cardiovasc Res. 2005. Vol. 67, No. 3. P. 367–378. DOI: 10.1016/j.cardiores.2005.03.005

[17] Felix R. Channelopathies: ion channel defects linked to heritable clinical disorders. J Med Genet. 2000;37(10):729–740.DOI: 10.1136/jmg.37.10.729

[18] Felix R. Channelopathies: ion channel defects linked to heritable clinical disorders // J Med Genet. 2000. Vol. 37, No. 10. P. 729–740. DOI: 10.1136/jmg.37.10.729

[19] Verkerk A, Wilders R, van Borren M, et al. Pacemaker current (If) in the human sinoatrial node. Eur Heart J. 2007;28(20):2472–2478. DOI: 10.1093/eurheartj/ehm339

[20] Verkerk A., Wilders R., van Borren M., et al. Pacemaker current (If) in the human sinoatrial node // Eur Heart J. 2007. Vol. 28, No. 20. P. 2472–2478. DOI: 10.1093/eurheartj/ehm339

[21] Bockeria OL, Akhobekov AA. Ion channels and their role in the development of arrhythmias. Annaly aritmologii. 2014;11(3):177–184. (In Russ.) DOI: 10.15275/annaritmol.2014.3.6

[22] Бокерия О.Л., Ахобеков А.А. Ионные каналы и их роль в развитии нарушений ритма сердца // Анналы аритмологии. 2014. Т. 11, № 3. С. 177–184.

[23] Grant A, Carboni M, Neplioueva V, et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest. 2002;110(8):1201–1209. DOI: 10.1172/JCI15570

[24] Grant A., Carboni M., Neplioueva V., et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation // J Clin Invest. 2002. Vol. 110, No. 8. P. 1201–1209. DOI: 10.1172/JCI15570

[25] Vibration model for hypoxic type of cell metabolism evaluated on rabbit cardiomyocytes. Bulletin of Experimental Biology and Medicine. 2009;147(6):712–715. (In Russ.)

[26] Воробьева В.В., Шабанов П.Д. Вибрационная модель гипоксического типа клеточного метаболизма, оцененная на кардиомиоцитах кролика // Бюллетень экспериментальной биологии и медицины. 2009. Т. 147, № 6. С. 712–715.

[27] Vorobieva VV, Shabanov PD. Cellular mechanisms of hypoxia development in the tissues of experimental animals under varying characteristics of vibration exposure. Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(3):59–70. (In Russ.)DOI: 10.17816/RCF17359-70

[28] Воробьева В.В., Шабанов П.Д. Клеточные механизмы формирования гипоксии в тканях экспериментальных животных на фоне варьирования характеристик вибрационного воздействия // Обзоры по клинической фармакологии и лекарственной терапии. 2019. Т. 17, № 3. С. 59–70. DOI: 10.17816/RCF17359-70

[29] Catterall WA, Chandy KG, Clapham DЕ, Perez-Reye Е. International union of pharmacology: Approaches to the nomenclature of voltage-gated ion channels. Pharmacol Rev. 2003;55(4):573–574. DOI: 10.1124/pr.55.4.8

[30] Catterall W.A., Chandy K.G., Clapham D.Е., Perez-Reye Е. International union of pharmacology: Approaches to the nomenclature of voltage-gated ion channels // Pharmacol Rev. 2003. Vol. 55, No. 4. P. 573–574. DOI: 10.1124/pr.55.4.8

[31] Zhang Z, Xu Y, Song H, et al. Functional Roles of Cav 1.3 (alpha1D) calcium channel in sinoatrial nodes: insight gainedusing gene targeted null mutant mice. Circ Res. 2002;90(9):981–987.DOI: 10.1161/01.res.0000018003.14304.e2

[32] Zhang Z., Xu Y., Song H., et al. Functional Roles of Cav 1.3 (alpha1D) calcium channel in sinoatrial nodes: insight gained using gene targeted null mutant mice // Circ Res. 2002. Vol. 90, No. 9. P. 981–987. DOI: 10.1161/01.res.0000018003.14304.e2

[33] Katz AM. Calcium channel diversity in the cardiovascular system. J Am Coll Cardiol. 1996;28(2):522–529.DOI: 10.1016/0735-1097(96)00170-2

[34] Katz A.M. Calcium channel diversity in the cardiovascular system // J Am Coll Cardiol. 1996. Vol. 28, No. 2. P. 522–529. DOI: 10.1016/0735-1097(96)00170-2

[35] Ginsburg KS, Bers DM. Modulation of excitation contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger. J Physiol. 2004;556(Pt2):463–480. DOI: 10.1113/jphysiol.2003.055384

[36] Ginsburg K.S., Bers D.M. Modulation of excitation contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger // J Physiol. 2004. Vol. 556, Pt 2. P. 463–480. DOI: 10.1113/jphysiol.2003.055384

[37] Reuter H, Han T, Motter C, et al. Mice overexpressing the cardiac sodium calcium exchanger: defects in excitation contraction coupling. J Physiol. 2004;554(Pt3):779–789. DOI: 10.1113/jphysiol.2003.055046

[38] Reuter H., Han T., Motter C., et al. Mice overexpressing the cardiac sodium calcium exchanger: defects in excitation contraction coupling // J Physiol. 2004. Vol. 554, Pt 3. P. 779–789.DOI: 10.1113/jphysiol.2003.055046

[39] Peterson BZ, Demaria CD, Adelman JP, et al. Calmodulin is the Ca2+ sensor for Ca2+ dependent inactivation of L type calcium channels. Neuron. 1999;22:549–558. DOI: 10.1016/s0896-6273(00)80709-6

[40] Peterson B.Z., Demaria C.D., Adelman J.P., et al. Calmodulin is the Ca2+ sensor for Ca2+ dependent inactivation of L type calcium channels // Neuron. 1999. Vol. 22, No. 3. P. 549–558.DOI: 10.1016/s0896-6273(00)80709-6

[41] Zuhlke RD, Pitt GS, Deisseroth K, et al. Calmodulin supports both inactivation and facilitation of L type calcium channels. Nature. 1999;399(6732):159–162. DOI: 10.1038/20200

[42] Zuhlke R.D., Pitt G.S., Deisseroth K., et al. Calmodulin supports both inactivation and facilitation of L type calcium channels // Nature. 1999. Vol. 399, No. 6732. P. 159–162. DOI: 10.1038/20200

[43] Bolli R, Marban E. Molecular and cellular mechanisms of myocardial stunning. Physiol Rev. 1999;79(2):609–634.DOI: 10.1152/physrev.1999.79.2.609

[44] Bolli R., Marban E. Molecular and cellular mechanisms of myocardial stunning // Physiol. Rev. 1999. Vol. 79, No. 2. P. 609–634. DOI: 10.1152/physrev.1999.79.2.609

[45] Carmeliet E. Cardiac ionic currents and acute ischemia: from channels to arrhythmias. Physiol Rev. 1999;79(3):917–1017. DOI: 10.1152/physrev.1999.79.3.917

[46] Carmeliet E. Cardiac ionic currents and acute ischemia: from channels to arrhythmias // Physiol. Rev. 1999. Vol. 79, No. 3.P. 917–1017. DOI: 10.1152/physrev.1999.79.3.917

[47] Coetzee WA, Amarillo Y, Chiu J, et al. Molecular diversity of K+ channels. Ann NY Acad Sci. 1999;868(1):233–255.DOI: 10.1111/j.1749-6632.1999.tb11293.x

[48] Coetzee W.A., Amarillo Y., Chiu J., et al. Molecular diversity of K+ channels // Ann NY Acad Sci. 1999. Vol. 868, No. 1. P. 233–255. DOI: 10.1111/j.1749-6632.1999.tb11293.x

[49] Nattel S, Li D. Ionic remodeling in the heart: pathophysiological significance and new therapeutic opportunities for atrial fibrillation. Circ Res. 2000;87(6):440–447. DOI: 10.1161/01.res.87.6.440

[50] Nattel S., Li D. Ionic remodeling in the heart: pathophysiological significance and new therapeutic opportunities for atrial fibrillation // Circ. Res. 2000. Vol. 87, No. 6. P. 440–447. DOI: 10.1161/01.res.87.6.440

[51] Hrynevich SV, Waseem TV, Fedorovich SV. Еstimation of the mitochondrial calcium pool in rat brain synaptosomes using Rhod-2 am fluorescent dye. Biophysics. 2017;62(1):75–78.DOI: 10.1134/S0006350917010079

[52] Hrynevich S.V., Waseem T.V., Fedorovich S.V. Еstimation of the mitochondrial calcium pool in rat brain synaptosomes using Rhod-2 am fluorescent dye // Biophysics. 2017. Vol. 62, No. 1. P. 75–78. DOI: 10.1134/S0006350917010079

[53] Leung AW, Waranyuwatana P, Halestrap AP. The mitochondrial phosphate carrier interacts with cyclophillin D and may play a key role in the permeability transition J Biol Chem. 2008;283(39):26312–26323. DOI: 10.1074/jbc M805235200

[54] Leung A.W., Waranyuwatana P., Halestrap A.P. The mitochondrial phosphate carrier interacts with cyclophillin D and may play a key role in the permeability transition // J Biol Chem. 2008. Vol. 283,No. 39. P. 26312–26323. DOI: 10.1074/jbc M805235200

[55] Raturi A, Simmen T. Where the endoplasmic reticulum and the mitochondrion the knot: the mitochondria-associated membrane (MAM). Biochim Biophys Acta. 2013;1833:213–224.DOI: 10.1016/j.bbamer.2012.04.013

[56] Raturi A., Simmen T. Where the endoplasmic reticulum and the mitochondrion the knot: the mitochondria-associated membrane (MAM) // Biochim. Biophys. Acta. 2013. Vol. 1833. P. 213–224. DOI: 10.1016/j.bbamer.2012.04.013

[57] Hirabayashi Y, Kwon SK, Paek H, et al. ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neuros. Sciens. 2017;358(6363):623–630. DOI: 10.1126/science.aan6009

[58] Hirabayashi Y., Kwon S.K., Paek H., et al. ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neuros // Sciens. 2017. Vol. 358, No. 6363. P. 623–630.DOI: 10.1126/science.aan6009

[59] Pogzig H, Becher C. Voltage-dependent cooperative in interactions between Сa2+-channel blocking drugs in intact cardiac cell.Annals NY Acad Sci. 1994;560:306–308.

[60] Pogzig H., Becher C. Voltage-dependent cooperative in interactions between Сa2+-channel blocking drugs in intact cardiac cell // Annals NY Acad Sci. 1994. Vol. 560. P. 306–308.

[61] Chen J, Devivo M, Dingus J, et al. A region of adenylatcyclase 2 critical for regulation by G protein βγ subunits. Sciense. 1995;268(5214):1166–1169. DOI: 10.1126/science.7761832

[62] Chen J., Devivo M., Dingus J., et al. A region of adenylatcyclase 2 critical for regulation by G protein βγ subunits // Sciense. 1995.Vol. 268, No. 5214. P. 1166–1169.

[63] Tkachuk VA, Avakian AE. Molecular mechanisms of G-Proteins with membrane receptors and second messenger systems. Russian Journal of Physiology. 2008;89(12):1478–1490.

[64] Tkachuk V.A., Avakian A.E. Molecular mechanisms of G-Proteins with membrane receptors and second messenger systems // Russian Journal of Physiology. 2008. Vol. 89, No. 12. P. 1478–1490.

[65] Abernethy DR, Soldatov J. Structure-functional diversity of human L-type Ca2+ channel: perspective for new pharmacological targets. J Pharmacol Exp Ther. 2002;300(3):724–728.DOI: 10.1124/jpet.300.3.724

[66] Abernethy D.R., Soldatov J. Structure-functional diversity of human L-type Ca2+ channel: perspective for new pharmacological targets // J Pharmacol Exp Ther. 2002. Vol. 300, No. 3. P. 724–728. DOI: 10.1124/jpet.300.3.724

[67] Widerberg А, Bergman S, Danielsen N, et al. Nerve injury induced by vibration: prevention of the effect of a conditioning lesion by D600, Сa2+ channel blocken. Occup Environ Med. 1997;54(5):312–315. DOI: 10.1136/oem.54.5.312

[68] Widerberg А., Bergman S., Danielsen N., et al. Nerve injury induced by vibration: prevention of the effect of a conditioning lesion by D600, Сa2+ channel blocken // Occup Environ Med. 1997. Vol. 54, No. 5. P. 312–315. DOI: 10.1136/oem.54.5.312

[69] Wappl E. Mechanism of dihydropyridine interaction with critical binding residues of L-type Ca2+ channel alpha 1 subunits. J Biol Chem. 2001;276(16):12730–12735. DOI: 10.1074/jbc.M010164200

[70] Wappl E. Mechanism of dihydropyridine interaction with critical binding residues of L-type Ca2+ channel alpha 1 subunits // J Biol Chem. 2001. Vol. 276, No. 16. P. 12730–12735. DOI: 10.1074/jbc.M010164200

[71] Casolo G, Stroder P, Rega L, et al. Regression of left ventricular hypertrophy after slow-release nifedipine administration in post-myocardial infarction patients (abstract). Eur Heart J. 1996;17:910–913.

[72] Casolo G., Stroder P., Rega L., et al. Regression of left ventricular hypertrophy after slow-release nifedipine administration in post-myocardial infarction patients (abstract) // Eur Heart J. 1996.Vol. 17. P. 910–913.

[73] Vorobieva VV, Shabanov PD. Exposure to whole body vibration impairs the functional activity of the energy producing system in rabbit miocardium. Biophysics. 2019;64(2):337–342.DOI: 10.1134/2FS0006350919020210

[74] Vorobieva V.V., Shabanov P.D. Exposure to whole body vibration impairs the functional activity of the energy producing system in rabbit myocardium // Biophysics. 2019. Vol. 64, No. 2. P. 337–342.DOI: 10.1134/2FS0006350919020210

[75] Kondrashova MN. Apparatura i poryadok raboty pri polyarograficheskom izmerenii dykhaniya mitokhondrii. Rukovodstvo po izucheniyu biologicheskogo okisleniya polyarograficheskim metodom. G.M. Frank, M.N. Kondrashovа, E.N. Mokhovа, Yu.S. Rotenberg, eds. Moscow: Nauka; 1973. P. 50–59. (In Russ.)

[76] Кондрашова М.Н. Аппаратура и порядок работы при полярографическом измерении дыхания митохондрий. Руководство по изучению биологического окисления полярографическим методом / под ред. Г.М. Франка, М.Н. Кондрашовой, Е.Н. Моховой, Ю.С. Ротенберг. Москва: Изд-во Наука, 1973. C. 50–59.

[77] Luk’yanova LD. Problemy gipoksii: molekulyarnye, fiziologicheskie i meditsinskie aspekty. Moscow; 2004. 520 с.(In Russ.)

[78] Лукьянова Л.Д. Проблемы гипоксии: молекулярные, физиологические и медицинские аспекты. Москва: Медицина, 2004. 520 с.

[79] Nikol’s D. Bioenergetika. Vvedenie v khemiosmoticheskuyu teoriyu. Moscow: Mir; 1985. 190 p. (In Russ.)

[80] Никольс Д. Биоэнергетика. Введение в хемиосмотическую теорию. Москва: Мир, 1985. 190 с.

[81] Skulachev VP, Bogachev AV, Kasparinskij FO. Membrannaya bioenergetika; Uchebnoe posobie Moscow: Moscow University Press; 2010. 368 p. (In Russ.)

[82] Скулачев В.П., Богачев А.В., Каспаринский Ф.О. Мембранная биоэнергетика: учебное пособие. Москва: Изд-во Московского университета, 2010. 368 с.

[83] Minkevich IG. The stoichiometry of metabolic pathways in the dynamics of cellular populations. Computer Research and Modeling. 2011;3(4):455–475. (In Russ.) DOI: 10.20537/2076-7633-2011-3-4-455-475

[84] Минкевич И.Г. Стехиометрия метаболических путей в динамике клеточных популяций // Компьютерные исследования и моделирование. 2011. Т. 3, № 4. С. 455–475.DOI: 10.20537/2076-7633-2011-3-4-455-475

[85] Adamantidis A, Arber S, Bains JS, et al. Optogenetics: 10 years after ChR2 in neurons — views from the community. Nat Neurosci. 2015;18(9):1202–1212. DOI: 10.1038/nn.4106

[86] Adamantidis A., Arber S., Bains J.S., et al. Optogenetics: 10 years after ChR2 in neurons — views from the community // Nat Neurosci. 2015. Vol. 18, No. 9. P. 1202–1212. DOI: 10.1038/nn.4106

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Vorobieva V.V., Levchenkova O.S., Shabanov P.D